Análisis del desempeño del lenguaje en sujetos con demencia tipo alzheimer (dta)

Antecedentes: la demencia tipo Alzheimer representaun 50-70% de las enfermedadesdemenciales. Su prevalencia es del 3-5% en personasmayores de 65 años y su incidencia de 1-2% al año en la población general; se caracterizapor alteraciones progresivas en la memoria, ellenguaje, la atención, el comportamiento y la presenciade déficit visoespaciales.Objetivo: hacer un análisis descriptivo-comparativode una muestra poblacional con demenciatipo Alzheimer, en especial una descripciónfenomenológica de las alteraciones del lenguajepresentes en esa población.Métodos: como criterios de inclusión se usaron:diagnóstico de demencia tipo Alzheimer, dominanciamanual derecha, escolaridad superior aquinto de primaria y capacidad para rendir laspruebas propuestas. Se comparó el rendimientoen las subpruebas de lenguaje del examenmínimo del estado mental (MMSE); en denominacióny fluidez semántica y fonológica y seanalizó el deterioro lingüístico en dos estadiosde la demencia tipo Alzheimer.Resultados: en el estadio leve se evidenciandéficit ligeros en todas las pruebas. Sinembargolos dominios con rendimiento más bajo fueronla fluidez fonológica y semántica. En el estadiomoderado se evidenciaron diferencias en el rendimiento;las tareas de denominación, fluidez semánticay fluidez fonológica tuvieron rendimientomás bajo.Conclusiones: el lenguaje es un dominio quesuele comprometerse en la demencia tipoAlzheimer. Los resultados reflejan el deterioroprogresivo de la habilidad lingüística, manifiestoen un amplio rango de frecuencia entre el estadio leve y el moderado de la demencia.Existe un perfil similar de deterioro para losestadios leve y moderado con patrones independientesen las pruebas específicas

The E6 Oncoprotein from HPV16 Enhances the Canonical Wnt/?-Catenin Pathway in Skin Epidermis In Vivo

The contribution of the Wnt signaling pathway to human papilloma virus (HPV)-induced carcinogenesis is poorly understood. In high-grade dysplastic lesions that are caused by high-risk HPVs (HR-HPV), ?-catenin is often located in the cell nucleus, which suggests that Wnt pathway may be involved in the development of HPV-related carcinomas. Most of the oncogenic potential of HR-HPVs resides on the PDZ-binding domain of E6 protein. We hypothesized that the PDZ-binding domain of the HPV16-E6 oncoprotein induces the nuclear accumulation of ?-catenin due to its capacity to degrade PDZ-containing cellular targets. To test this hypothesis, we evaluated the staining pattern of ?-catenin in the skin epidermis of transgenic mice expressing the full-length E6 oncoprotein (K14E6 mice) and measured LacZ gene expression in K14E6 mice that were crossed with a strain expressing LacZ that was knocked into the Axin2 locus (Axin2+/LacZ mice). Here, we show that the E6 oncoprotein enhances the nuclear accumulation of ?-catenin, the accumulation of cellular ?-catenin–responsive genes, and the expression of LacZ. None of these effects were observed when a truncated E6 oncoprotein that lacks the PDZ-binding domain was expressed alone (K14E6?PDZ mice) or in combination with Axin2+/LacZ. Conversely, cotransfection with either E6 or E6?PDZ similarly enhanced canonical Wnt signaling in short-term in vitro assays that used a luciferase Wnt/?-catenin/TCF-dependent promoter. We propose that the activation of canonical Wnt signaling could be induced by the HPV16-E6 oncoprotein; however, the participation of the E6 PDZ-binding domain seems to be important in in vivo models only. Mol Cancer Res; 10(2); 250–8. ©2011 AACR

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019 : A systematic analysis for the Global Burden of Disease Study 2019

Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Análisis del desempeño del lenguaje en sujetos con demencia tipo Alzheimer (DTA)

Antecedentes: la demencia tipo Alzheimer representa un 50-70% de las enfermedades demenciales. Su prevalencia es del 3-5% en personas mayores de 65 años y su incidencia de 1- 2% al año en la población general; se caracteriza por alteraciones progresivas en la memoria, el lenguaje, la atención, el comportamiento y la presencia de déficit visoespaciales. Objetivo: hacer un análisis descriptivo-comparativo de una muestra poblacional con demencia tipo Alzheimer, en especial una descripción fenomenológica de las alteraciones del lenguaje presentes en esa población. Métodos: como criterios de inclusión se usaron: diagnóstico de demencia tipo Alzheimer, dominancia manual derecha, escolaridad superior a quinto de primaria y capacidad para rendir las pruebas propuestas. Se comparó el rendimiento en las subpruebas de lenguaje del examen mínimo del estado mental (MMSE); en denominación y fluidez semántica y fonológica y se analizó el deterioro lingüístico en dos estadios de la demencia tipo Alzheimer. Resultados: en el estadio leve se evidencian déficit ligeros en todas las pruebas. Sinembargo los dominios con rendimiento más bajo fueron la fluidez fonológica y semántica. En el estadio moderado se evidenciaron diferencias en el rendimiento; las tareas de denominación, fluidez semántica y fluidez fonológica tuvieron rendimiento más bajo. Conclusiones: el lenguaje es un dominio que suele comprometerse en la demencia tipo Alzheimer. Los resultados reflejan el deterioro progresivo de la habilidad lingüística, manifiesto en un amplio rango de frecuencia entre el estadio leve y el moderado de la demencia. Existe un perfil similar de deterioro para los estadios leve y moderado con patrones independientes en las pruebas específicas

Analysis of language performance in subjects with Alzheimer's dementia (ATD)

Antecedentes: la demencia tipo Alzheimer representa un 50-70% de las enfermedades demenciales. Su prevalencia es del 3-5% en personas mayores de 65 años y su incidencia de 1-2% al año en la población general; se caracteriza por alteraciones progresivas en la memoria, el lenguaje, la atención, el comportamiento y la presencia de déficit visoespaciales. Objetivo: hacer un análisis descriptivo-comparativo de una muestra poblacional con demencia tipo Alzheimer, en especial una descripción fenomenológica de las alteraciones del lenguaje presentes en esa población. Métodos: como criterios de inclusión se usaron: diagnóstico de demencia tipo Alzheimer, dominancia manual derecha, escolaridad superior a quinto de primaria y capacidad para rendir las pruebas propuestas. Se comparó el rendimiento en las subpruebas de lenguaje del examen mínimo del estado mental (MMSE); en denominación y fluidez semántica y fonológica y se analizó el deterioro lingüístico en dos estadios de la demencia tipo Alzheimer. Resultados: en el estadio leve se evidencian déficits ligeros en todas las pruebas. Sin embargo, los dominios con rendimiento más bajo fueron la fluidez fonológica y semántica. En el estadio moderado se evidenciaron diferencias en el rendimiento; las tareas de denominación, fluidez semántica y fluidez fonológica tuvieron rendimiento más bajo. Conclusiones : el lenguaje es un dominio que suele comprometerse en la demencia tipo Alzheimer. Los resultados reflejan el deterioro progresivo de la habilidad lingüística, manifiesto en un amplio rango de frecuencia entre 4 Análisis del lenguaje en sujetos con demencia el estadio leve y el moderado de la demencia. Existe un perfil similar de deterioro para los estadios leve y moderado con patrones independientes en las pruebas específicas.Background: Alzheimer disease explains near 70% of all instances of dementia and its prevalence in 65 years old population is 3-5% while incidence is near 1-2 % per year in general population. The clinical features of alzheimer disease are essentially: memory deficits and changes in language, behavior, attention and loss of visuospatial skills. Objetive: to make a descriptive analysis of the performance in language skills in 23 Alzheimer disease subjects. Methods: subjects were included if: meet Alzheimer disease criteria; right handed; a minimal of five years of formal school and were able to complete the language tests. We dichotomize the group in mild and moderate according to global deterioration scale (GDS) and clinical dementia rating (CDR) classification. The performance in the subtests of language of the Minimal Mental State Examination (MMSE), denomination, semantic and phonological fluency was compared between groups. The linguistic deterioration was analyzed in both steps of DTA. Results: in the mild stadium, light deficits are demonstrated in all the tests. Nevertheless, dominium with poorer performance were phonological and semantic fluency . In moderate state differences in performance were observed. Tasks on denomination, and semantic and phonological fluency had the poorer performance. Conclusion: language is a compromised neuropsychological dominium in Alzheimer disease. Our results reflect a progressive deterioration of linguistic skills, noted in a wide range of frequency between the mild and the moderated level of dementia and suggests a similar profile of deterioration in mild and moderate levels but with different patterns in specific tasks

Analysis of language performance in subjects with Alzheimer's dementia (ATD)

Antecedentes: la demencia tipo Alzheimer representa un 50-70% de las enfermedades demenciales. Su prevalencia es del 3-5% en personas mayores de 65 años y su incidencia de 1-2% al año en la población general; se caracteriza por alteraciones progresivas en la memoria, el lenguaje, la atención, el comportamiento y la presencia de déficit visoespaciales. Objetivo: hacer un análisis descriptivo-comparativo de una muestra poblacional con demencia tipo Alzheimer, en especial una descripción fenomenológica de las alteraciones del lenguaje presentes en esa población. Métodos: como criterios de inclusión se usaron: diagnóstico de demencia tipo Alzheimer, dominancia manual derecha, escolaridad superior a quinto de primaria y capacidad para rendir las pruebas propuestas. Se comparó el rendimiento en las subpruebas de lenguaje del examen mínimo del estado mental (MMSE); en denominación y fluidez semántica y fonológica y se analizó el deterioro lingüístico en dos estadios de la demencia tipo Alzheimer. Resultados: en el estadio leve se evidencian déficits ligeros en todas las pruebas. Sin embargo, los dominios con rendimiento más bajo fueron la fluidez fonológica y semántica. En el estadio moderado se evidenciaron diferencias en el rendimiento; las tareas de denominación, fluidez semántica y fluidez fonológica tuvieron rendimiento más bajo. Conclusiones : el lenguaje es un dominio que suele comprometerse en la demencia tipo Alzheimer. Los resultados reflejan el deterioro progresivo de la habilidad lingüística, manifiesto en un amplio rango de frecuencia entre 4 Análisis del lenguaje en sujetos con demencia el estadio leve y el moderado de la demencia. Existe un perfil similar de deterioro para los estadios leve y moderado con patrones independientes en las pruebas específicas.Background: Alzheimer disease explains near 70% of all instances of dementia and its prevalence in 65 years old population is 3-5% while incidence is near 1-2 % per year in general population. The clinical features of alzheimer disease are essentially: memory deficits and changes in language, behavior, attention and loss of visuospatial skills. Objetive: to make a descriptive analysis of the performance in language skills in 23 Alzheimer disease subjects. Methods: subjects were included if: meet Alzheimer disease criteria; right handed; a minimal of five years of formal school and were able to complete the language tests. We dichotomize the group in mild and moderate according to global deterioration scale (GDS) and clinical dementia rating (CDR) classification. The performance in the subtests of language of the Minimal Mental State Examination (MMSE), denomination, semantic and phonological fluency was compared between groups. The linguistic deterioration was analyzed in both steps of DTA. Results: in the mild stadium, light deficits are demonstrated in all the tests. Nevertheless, dominium with poorer performance were phonological and semantic fluency . In moderate state differences in performance were observed. Tasks on denomination, and semantic and phonological fluency had the poorer performance. Conclusion: language is a compromised neuropsychological dominium in Alzheimer disease. Our results reflect a progressive deterioration of linguistic skills, noted in a wide range of frequency between the mild and the moderated level of dementia and suggests a similar profile of deterioration in mild and moderate levels but with different patterns in specific tasks

COVIDiSTRESS diverse dataset on psychological and behavioural outcomes one year into the COVID-19 pandemic

During the onset of the COVID-19 pandemic, the COVIDiSTRESS Consortium launched an open-access global survey to understand and improve individuals’ experiences related to the crisis. A year later, we extended this line of research by launching a new survey to address the dynamic landscape of the pandemic. This survey was released with the goal of addressing diversity, equity, and inclusion by working with over 150 researchers across the globe who collected data in 48 languages and dialects across 137 countries. The resulting cleaned dataset described here includes 15,740 of over 20,000 responses. The dataset allows cross-cultural study of psychological wellbeing and behaviours a year into the pandemic. It includes measures of stress, resilience, vaccine attitudes, trust in government and scientists, compliance, and information acquisition and misperceptions regarding COVID-19. Open-access raw and cleaned datasets with computed scores are available. Just as our initial COVIDiSTRESS dataset has facilitated government policy decisions regarding health crises, this dataset can be used by researchers and policy makers to inform research, decisions, and policy.</jats:p